2-methoxy-3-methyl-5, 6-dichloro-benzoates



3,913,061 2=hETHOXY-3-METHYL-5,6=DICHLORO- 3ENZOATES Sidney B. Richter,Chicago, Ill., assignor to Veisicol (Ihernical Corporation, Chicago,IlL, a corporation of Illinois No Drawing. Filed Nov. 28, 1958, Ser. No.776,717 12 Claims. (Cl. 260473) This invention relates to new herbicidalcompositions of matter. More specifically, this invention relates to thecontrol of undesirable plant life with 2-methoxy-3-methyl-5,o-dichlorobenzoic acid, its anhydride, its amides, its esters,its alkali metal salts, or its amine salts.Z-methoxy-3-methyl-5,6-dichlorobenzoic acid, which has the structure(FOOH O1- C.Ha

will hereinafter be referred to as compound I. This chemical compoundand its derivatives as cited above have marked activity as herbicidesuseful for the con trol of undesirable plant life.

Compound I can be prepared readily, for example, fro-m the knowncompound 3-methyl-5-chlorosalicylic acid. This compound is chlorinatedfurther in the 6-position to give 3-methyl-5,6-dichlorosalicyclic acid.The chlorination can be effected with gaseous chlorine in the presenceof fuming sulfuric acid. The resulting 3-methyl- 5,6-dichlorosalicylicacid is then converted to one of its alkali metal salts and treated withan excess of dimethyl sulfate in basic medium. The dimethyl sulfate ispreferably added to the reaction mixture with ice cooling, but thereaction mixture is refluxed to complete the reaction. Additional alkalimetal hydroxide solution is added, and the reaction mixture is againrefluxed to hydrolyze any carboxylic acid ester which may have formed.The cooled reaction mixture is then acidified with a mineral acid suchas hydrochloric acid, and the solid which separates is filtered, washedwith cold water, and dried to give compound I. The compound I obtainedin this manner is suitable for many herbicidal uses as such, but ifdesired it can be purified, as by recrystallization from a suitablesolvent.

The anhydride of compound I is prepared by the removal of one moleculeof water from two molecules of compound I as the free acid. In practice,it is convenient to prepare the anhydride by the acylation of the freecarboxylic acid by its acid halide in the presence of a strong acylatingagent such as pyridine. Thus a mixture of dry pyridine and dry benzeneare treated with 1 mole of the acid chloride of compound I. The slightlyexothermic reaction proceeds with the formation of an intermediatepyridinium salt. One mole of compound I as the free acid is then added,the precipitate of pyridine hydrochloride is removed, and the anhydrideof compound I is isolated by removal of the benzene.

The acid halide of compound I required in the above and other synthesesis prepared by the reaction of the free acid with a phosphoroustrihalide in the conventional manner. Thus the treatment of compound Iwith phosphorous trichloride until the reaction ceases produces the acidchloride of compound I. 7

Compounds which are salts, esters, or amides of compound I can beprepared readily from the free acid. 'Ihus treatment of the free acidwith ammonium hydroxide gives a product which is the salt ammonium2-methoxy-3methyl-5,fi-dichlorobenzoate. Similarly, an alkali metal saltof compound I can be made by the Patented Dec. 12 1961 amine,triethanolamine, isopropylamine, morpholine, and

the like. The resulting products are, respectively, the dim-ethylamine,trimethylamine, triethylamine, diethanolamine, triethanolamine,isopropylamine, and morpholine salts of2-methoxy-3-methyl-5,6-dichlorobenzoic acid.

Esters of compound I are prepared by the condensation of the acid withvarious alcohols. Thus the condensation of methyl alcohol with compoundI gives the desired ester, methylZ-methoxy-3-methyl-5,6-dichlorobenzoate. Other typical alcohols whichcan be used are propyl, isop-ropyl, n-butyl, sec-butyl, isobutyl,tert-butyl, amyl, hexyl, heptyl, octyl, nonyl, decyl and the like. Theproducts are the corresponding alkyl esters of2-methoxy-3-methyl-5,6-dichlorobenzoic acid. Although such complexesters as thos prepared by the esterification of compound I withbutoxyethanol, propylene glycol butyl ether, and the like are usefulproducts in accordance with this invention, preferred esters are thosein which the esterifying group is an unsubstituted alkyl group whichcontains from 1 to 10 carbon atoms. The condensation of the acid withthe alcohol is carried out suitably in an inert solvent such as anaromatic hydrocarbon and in the presence of a few percent by weight ofan acid catalyst such as p-toluenesulfonic acid. The water which formsduring the esterification reaction can be removed continuously in manycases from the reaction mixture by distillation as it forms, and itsvolume can be measured to determine when the esterification is complete.The ester is then isolated by distillation of the inert solvent. 7

Amides of compound I can be prepared conveniently by the reaction of theacid halide of compound I with ammonia or various amines. The reactioncan be carried out in an inert solvent such as ether or benzene.Preferably two moles of the amine are used for each mole of the acidhalide employed, since the hydrogen halide released during the reactionis taken up by some of the free amine which remains. The simplest amide,Z-methoxy-3-methyl-5,6-dichlorobenzamide, can be prepared by thereaction of the acid chloride of compound I with ammonia, either as thefree gas or asan aqueous solution. This amide can alsobe prepared byhydrolysis of the corresponding nitrile. Substituted amides arepreparedby the reaction of the acid halide of compound I with amines such as anyof the primary or secondary amines suggested above for the preparationof ,the amine salts of compound I. Thus, for example, the reaction ofthe acid chloride of compound I with methylamine, butylamine,decylamine, or dimethylamine gives the -N-methyl-, N-butyl-, N-decyl-,or N,N-diethyl-2-methoxy- 3-methyl-5,o-dichlorobenzamides, respectively.While more complex amines such as the aromatic amines can be used as theamine reactant to givedesirable products, which are specifically namedas anilides, preferred amine reactants are alkylamines containing up to10 carbon atoms.

For practical use as herbicides, the compounds of this invention areformulated with inert carriers to obtain proper concentrations and tofacilitate handling. For example, these compounds can be formulated intodusts by combining them with such inert substances as talc or clays. Thealkali metal salts of compound I are particdust formulations, and dustscontaining from to '25 percent by weight of active compound areconvenient for use in the field. The compounds of this invention,however, are preferably applied as sprays. These can be made as simplesolutions by dissolving the compounds in organic solvents such asxylene, kerosene, or the methylated naphthalenes. The esters of compoundI, which ordinarily are liquids at room temperature, are particularlysuited to formulation by this method. The amine salts of compound Ioften show good solubility in water and can aqueous solutions.

The compounds of this invention can also be emulsified or suspended inwater by the addition of emulsifiers and wetting agents. Theformulations of these active herbicidal compounds are either applieddirectly to the plants to be controlled, 'or the soil in which theplants are growing can be treated. Substances such as other pesticides,stabilizers, activators, synergists, spreaders and adhesives can beadded to the formulations if desired. There is no significant differencein effect from the amount of Water or organic solvent for diluting theseherbicides, providing the same amount of chemical is distributed evenlyover a given area. Such distribution can be ob tained, for example, withlow-pressure, low-volume sprays at the rate of about gallons of sprayper acre.

In applying the herbicidal compounds, consideration must be given to thenature and stage of growth of the crop, the species of Weeds present,the stage of growth of the Weeds, environmental factors influencing therate and vigor of the weed growth, weather conditions at the time ofapplication and immediately following, and the dosage to be applied to agiven area. Weeds are most susceptible when they are small and growingrapidly. Early application, therefore, results in better control withless chemical and increased yields because of the early destruction ofthe competing weeds. The larger and older the weeds the higher theconcentration needed to kill them. Summer annuals such aslambs-quarters, pigweeds, cocklebur, and sunflower should be sprayedwhen they are less than 4 inches high. Winter annuals such as variousmustards, fan-weed, yellow star-thistle, and wild radish are most easilykilled while they are still in the rosette stage. Usually weeds growingrapidly under optimum conditions are relatively susceptible, whereasthose growing under adverse conditions tend to be resistant to theherbicide sprays.

The effectiveness of the compounds of thi invention in small quantitiesmakes them economically sound for weed control on large areas, with agreat saving in labor and cost, in addition to corresponding cropincreases. These compounds are particularly valuable in weed controlbecause they are harmful to many weeds but harmless or relativelyharmless to some cultivated crops. Minute quantities in contact withplant tissues may be absorbed and translocated to all parts of theplant, causing striking changes in the form and functions and oftenularly suited to such be used directly as resulting in their death. Theactual amount of compound to be used depends on a variety of factors butis influenced primarily by the species of undesirable plant to becontrolled. Thus while fractions of a pound of actual compound I or itsequivalent of an ester, salt, amide, or the anhydride of compound I areoften sufiicient for post emergence weed control on an acre of corn,seed flax, perennial grass seed crops, pastures or grazing areas(without legumes), heat, and the like,'the particular species of weedsencountered in evergreen and decidous I dormant nursery stock, nurseryconifers, waste areas, woody brush, and the like may require'the use ofone or more pounds'of compound I or its derivatives per acre for goodcontrol. Dosage adjustments with the lowvolume, low-pressureapplications suggested can be made by changing the nozzle size, nozzlespacing, pressure, or traveling rate of thespray equipment.

The manner in which the herbicidal compounds ofthis 7 EXAMPLE 1Preparation of 3-methyl-5,6-dichlorosalicylic acid3-methyl-5-chlorosalicylic acid (1.61 moles), which can be obtained, forexample, as described by Mowry, Yanko, and Ringwald in the J. Am. Chem.Soc., vol. 69, pp. 2358-61 (1947), is added slowly and carefully to 1liter of fuming sulfuric acid in a 2-liter, round-bottomed flask fittedwith a reflux condenser, internal thermometer, mechanical stirrer, andgas inlet tube. Chlorine gas is passed into the reaction mixture over aperiod of 15 hours while the pot temperature is maintained at -90 C. The reaction mixture is then cooled to room tempera ture and pouredslowly onto 3 liters of crushed ice. The solid is filtered, washed withcold water, pressed dry, and dried completely in a vacuum oven to give3-methyl-5,6- dichlorosalicylic acid.

EXAMPLE 2 Preparation of 2-methoxy-3-methyl-5,6-dichlorobenzoic acid(compound I) 3-methyl-5,6-dichlorosalicylic acid (1.04 moles) isdissolved in a solution of sodium hydroxide (232 g.; 5.8 moles) in 1400ml. of water in a 3-liter, round-bottomed flask fitted with a mechanicalstirrer, reflux condenser, internal thermometer, and addition funnel.The flask is packed in ice, and the reaction mixture is cooled to 20 C.Dimethyl sulfate (366 g.; 2.9 moles) is added with rapid stirring, andthe mixture is stirred for 20 minutes at a temperature below 35 C. Asecond portion of dimethyl sulfate (366 g.) is added, and the mixture isstirred for 10 minutes at a temperature below 45 C. The reaction mixtureis then stirred and refluxed for 2 hours, whereupon a solution of sodiumhydroxide (116 g.) in 400 ml. water is added, and the mixture isrefluxed for an addi tional 2 hours. The mixture is then cooled andacidified to Congo red indicator with hydrochloric acid. Theprecipitated solid is filtered, washed with cold water, pressed dry, anddried completely in a vacuum oven to give compound I.

EXAMPLE 3 Preparation of the sodium salt of compound I Preparation ofthe ammonium salt of compound 1 Treatment of compound I (0.5 mole) in500 cc. of methanol with 34 cc. of commercial concentrated ammoniumhydroxide according to the method given in the previous example givesthe desired ammonium salt of compound I.

EXAMPLE 5 Preparation of the dimethylamine salt of compound 1 Compound I(0.5 mole) is dissolved in 500 cc. of dry ether and treated withdimethylamine (22.5 g.; 0.5 mole). The solid which separates isfiltered, washed twice with cc. portions of cold ether, filtered,pressed dry, and dried completely in a vacuum oven to give the desireddimethylamine salt of compound I.

EXAMPLE 6 Preparation of the diethanolamine salt of compound I In themanner described in the previous example, compound I (0.5 mole) istreated with diethanolamine (52.5 g.; 0.5 mole) in 500 cc. of dry ether.The product which is isolated is the diethanolarnine salt of compound I.

EXAMPLE 7 Preparation of the morpholine salt of compound I Compound I(0.5 mole) is treated with morpholine (43.5 g.; 0.5 mole) in 500 cc. ofether, and the product is worked up as described for the preparation ofthe dimethylamine salt to give the desired morpholine salt of compound1.

EXAMPLE 8 Preparation of the ethyl ester of compound I Compound I (0.5mole), ethyl alcohol (23 g.; 0.5 mole), and 3.0 g. of p-toluenesulfonicacid are dissolved in 500 ml. of benzene, and the solution is placed ina 1- liter, round-bottomed flask fitted with a reflux condenser and acalibrated Dean-Stark tube. The solution is heated at reflux temperatureuntil 9 cc. of water have been collected in the Dean-Stark tube. Thecooled reaction mixture is then extracted twice with 50-cc. portions of10% sodium carbonate solution, and filtered. The benzene is distilledofi in vacuo on the steam bath, and the residue is then distilled invacuo to give the desired ethyl ester of compound I.

EXAMPLE 9 Preparation of the decyl ester of compound I In the manner andapparatus described in the previous example, compoundl (0.5 mole) andnormal primary decyl alcohol (79 g.; 0.5 mole) are refluxed in 500 ml.of benzene in the presence of 3.0 g. of p-toluenesulfonic acid until 9cc. of Water have been distilled from the reaction mixture. Work-up ofthe reaction mixture as described in the previous example gives thedesired decyl ester of compound 1.

EXAMPLE 10 Preparation of the n-butyl ester of compound I The reactionof compound I (0.5 mole) and n-butyl alcohol (37 g. 0.5 mole) by themethod described above for the preparation of the ethyl ester is used toprepare the n-butyl ester of compound 1.

EXAMPLE 11 Preparation of the acid chloride of compound I Compound I (1mole) is placed With 500 cc. of dry benzene in a 2-liter, 3-necked,round bottomed flask fitted with a mechanical stirrer, reflux condenser(calcium chloride tube), and dropping funnel. Phosphorus trichloride(123 g.; 0.9 mole) is added slowly dropwise with vigorous stirring whilethe reaction flask is cooled with cold water if necessary to control thereaction. When all the PCI;, has been added and the evolution ofhydrogen chloride has ceased, the reaction mixture is then transferredto distillation apparatus, and the solvent is distilled off. The residueis then distilled in vacuo to give the desired acid chloride of compoundI.

EXAMPLE 12 Preparation of the amide of compound I One mole of the acidchloride of compound I is placed with 500 cc. of dry benzene in a1-liter, 3-necked flask fitted with a reflux condenser, mechanicalstirrer, and a gas inlet tube having a sparger tip. The mixture isstirred while dry ammonia gas is passed into the mixture for severalhours. When the ammonia gas is no longer taken up, the precipitated saltis filtered off and extracted twice With 100 ml. portions of ether. Theether extracts and benzene filtrate are dried over magnesium sulfate andfiltered, and the solvents are distilled off to give the desired amideof compound I.

6 EXAMPLE 13 Preparation of the N-n-decylamide of compound I salt isfiltered off and extracted with two ml. pertions of ether. The etherextracts and benezene filtrate are dried over magnesium sulfate andfiltered. Distillation of the solvents gives the desired N-n-decylamideof compound I.

EXAMPLE 14 Preparation of the N,N-diethylamide of compound 1 One mole ofthe acid chloride of compound I is treated with diethylamine (146 g.;2.0 moles) in the manner and apparatus described in the previous exampleto give the N,N-diethylamide of compound I.

EXAMPLE 15 Preparation of the anhydride of compound I Dry pyridine (158g.; 2.0 moles) and 1 liter of dry benzene are placed in a 2-liter,3-necked, round-bottom flask fitted with a dropping funnel, mechanicalstirrer, reflux condenser, and internal thermometer. One mole of theacid chloride of compound I, which is prepared as described in aprevious example, is added rapidly with stirring to the reactionmixture. Compoundl (1 mole) is then added in portions over a period ofabout 10 minutes with rapid stirring. The pyridine hydrochloride whichprecipitates is filtered off, and the benzene is distilled from thefiltrate in vacuo. The residue contains the desired anhydride ofcompound I, which can be purified by crystallization from a suitablesolvent.

EXAMPLE 16 Preparation of an emulsifiable concentrate of compound I Thefollowing concentrate is prepared by mixing the ingredients intimatelyin the given percentage proportions by weight:

Percent Compound! 25 Antarox A-400 40 Methanol 35 Antarox A-400 is thetrade name under which a nonionic detergent of the aromatic polyethyleneglycol ether type is sold. The above concentrate is diluted with waterto the desired concentration for use.

EXAMPLE 17 Preparation of an emulsifiable concentrate of the n-butylester of compound I The following ingredients are mixed thoroughly inthe given percentage proportions by weight:

Triton X100 is the trade name under which an emulsifier of the alkylaryl polyether alcohol type is sold. The above concentrate is dilutedwith Water to the desired concentration for use.

7 EXAMPLE 18 Preparation of a dust from the sodium salt of compound IThe sodium salt of compound I (10% by weight) and talc (90% by weight)are combined and ground to the desired particle size in a mechanicalgrinder blender.

The herbicidal activity of chemical compounds is often demonstrated bythe ability of the chemicals to kill or arrest the growth of tomatoplants. The tomato plant is readily grown and maintained under uniformconditions for experimental purposes in greenhouses, and its response tochemicals is very similar to that observed for a wide variety ofeconomically important species of undesirable plant life in the field.

The herbicidal activity of the compounds of this invention, for example,can be demonstrated in greenhouse experiments on young potted tomatoplants (Bonny Best variety). The compounds are formulated into 10percent wettable powders and are dispersed in water at a concentrationof 2,000 parts per million actual chemical. Ten milliliters of analiquot portion of the dispersion is added to the soil surface of thetomato plants, approximately to 7 inches tall. In order to avoid undueconcentration or accumulation of the chemical in any given area, 5 holesthe size of a pencil and about 1 inch deep are punched in the soilsurface around the shoot, and the milliliter application is dividedequally among the 5 holes. Three plants are used for each ap plication.The treated plants are held under greenhouse conditions for 7 days,provided with subterranean watering, and observed for response totreatment. The results indicate a high order of herbicidal toxicity ofthe compounds of this invention.

1 claim as my invention:

1. A compound selected from the group consisting of2-methoxy-3-methyl-5,6-dichlorobenzoie acid, its anhydride, its alkalimetal salts, its ammonium salt, its morpholine salt, its alkyl aminesalts in which the amine component is an unsubstituted alkyl amine of upto six carbon atoms, its alkanol amine salts in which the aminecomponent is an unsubstituted alkanol amine of up to six carbon atoms,its esters in which the esterifying group is an unsubstituted alkylgroup of from one to ten carbon atoms, its butoxyethanol ester, itsunsubstituted amide,

and its alkyl amides in which the amine component is an unsubstitutedalkyl amine of up to ten carbon atoms. I p I 2. An alkali metal salt of2-methoXy-3-methyl-5,6-dichlorobenzoic acid.

5 3. An alkyl amine salt of 2-methoxy-3-methyl-5,6-dichlorobenzoic acidin which the amine component is an unsubstituted alkyl amine of up tosix carbon atoms.

4. An ester of 2-methoxy-3-methyl-5,6-dichlorobenzoie acid, in which theesterifying group is an unsubstituted 10 alkyl group of from one to tencarbon atoms.

5. An alkyl amide of 2-methoXy-3-methyl-S,6-dichlorobenzoic acid inwhich the amine component is an unsubstituted alkyl amine of up to tencarbon atoms.

6. An alkanol amine salt of 2-methoxy-3-methyl-5,6-

dichlorobonzoic acid in which the amine component is an unsubstitutedalkanol amine of up to six carbon atoms.

7. The dimethylamine salt of 2-methoxy-3-methyl-5,6- dichlorobenzoicacid.

8. 2-methoxy-3-methyl-5,6-dichlorobenzoic acid.

9. Sodium 2-rnethoxy-3-methyl-5,6-dichlorobenzoate.

10. The diethanolamine salt of 2-methoxy-3-rnethyl- 5,6-dichlorobenzoicacid. I

11. n-Butyl 2-methoxy-3-methyl-5,6-dichlorobenzoate.

l2. Bis(2 methoxy-3-methyl-5,6-dichlorobenzoic) anhydride.

References Cited in the file of this patent UNITED STATES PATENTSOkazaki et al.: J. Pharm. Soc., 72, 1941 (1952). Muir et al.: Chem.Abst., 47, 9435 (1953).

Brockmann et al.: Chem. Abst., 50, 7803 (1956).

1. A COMPOUND SELCTED FROM THE GROUP CONSISTING OF2-METHOXY-3-METHYL-5,6-DICHLOROBENZOIC ACID, ITS INHYDRIDE, ITS ALKALIMETAL SALTS, ITS AMMONIUM SALT, ITS MORPHOLINE SALT, ITS ALKYL AMINESALTS IN WHICH THE AMINE COMPONENT IS AN UNSUBSTITUTED ALKYL AMINE OF UPTO SIX CARBON ATOMS, ITS ALKANOL AMINE SALTS IN WHICH THE AMINECOMPONENT IS AN UNSUBSTITUTED ALKYL AMINE OF UP TO SIX CARBON ATOMS, ITSESTERS IN WHICH THE ESTERIFYING GROUP IS AN UNSUBSTITUTED ALKYL GROUP OFFROM ONE TO TEN CARBON ATOMS, ITS BUTOXYETHANOL ESTER, ITS UNSUBSTITUTEDAMIDE,, AND ITS ALKYL AMIDES IN WHICH THE AMINE COMPONENT IS ANUNSUBSTITUTED ALKYL AMINE OF UP TO TEN CARBON ATOMS.
 4. AN ESTER OF2-METHOXY-3-METHYL-5,6-DICHLOROBENZOIC ACID, IN WHICH THE ESTERIFYINGGROUP IS AN UNSUBSTITUTED ALKYL GROUP OF FROM ONE TO TEN CARBON ATOMS.